Narendra  Wajapeyee, Ph.D.

Training:

B.S. Kanpur University, Kanpur, India
M.S. Guru Nanak Dev University, Amritsar, India
Ph.D. Indian Institute of Science, Bangalore, India
Post-doctoral Training: Program in Gene Function Expression, University of Massachusettes Medical School, Worcester, MA with Prof. Michael R Green, HHMI.

Expertise:

Cancer Genetics and High-throughput Genomics.

Research Interests:

Cancer is a complex disease and typically involves multiple gene-specific and global genetic and epigenetic changes in human genome. The major class of genes that has been causally linked to the process of tumorigensis is tumor suppressors, which acts as a "breaks" and oncogenes, which functions as "accelerators" and typically promotes cancer. Recently, microRNAs are also linked to cancer wherein they can function either as tumor suppressors or oncogenes. The focus of our lab is to understand the mechanisms of genetic and epigenetic regulation of cancer causing genes and translating this understanding for early detection and treatment of human cancers.

In a recent study we have analyzed leukemogenic fusion-proteins. Hematological malignancies are typically associated with leukemogenic fusion-proteins, which are required to maintain the oncogenic state. Previous studies have shown that certain oncogenes that promote solid tumors, such as RAS and BRAF, can induce senescence in primary cells, which is thought to provide a barrier to tumorigenesis. In these cases the activated oncogene elicits a DNA damage response (DDR), which is essential for the senescence program. We observed that three leukemogenic fusion-proteins, BCR-ABL, CBFB-MYH11 and RUNX1-ETO, can induce senescence in primary fibroblasts and hematopoietic progenitors. Unexpectedly, we found that senescence induction by BCR-ABL and CBFB-MYH11 occurs through a DDR-independent pathway, whereas RUNX1-ETO induces senescence in a DDR-dependent manner. Our results reveal diverse pathways for oncogene-induced senescence and further suggest that leukemias harbor genetic or epigenetic alterations that inactivate senescence induction genes.

Currently, experiments are underway to identify and validate the secondary genetic hits that might cooperate with oncogenic fusion proteins.

Professional Service:

Selected Publications: